Ageotypes, Sex and Individual Differences in Longevity


Your Ageotype: How You Age, Individually

Ageing biology is mind-blowingly complex.

Stepping back from the minute details and thousands of interacting molecular pathways, we age in broad categories.

Stanford Professor Michael Snyder coined the term ‘Ageotypes’.

It describes four broad categories of ageing. They are metabolic ageing, immune aging and specific ageing for liver and kidney functions. You have a unique profile of how you age in each category – and may be biologically older in one or more areas than the others.

There are sex differences to consider too.

Mouse studies show variable results for longevity drugs and treatments including calorie restriction is different for female and male mice. Around the world, human females live longer than males independently of socioeconomic factors.

Gene differences also affect longevity. A well-studied example is the APOE gene – which shortens life expectancy by making carriers more prone to Alzheimer’s and Dementia.

This page introduces the concept of Ageotypes, sex and individual differences in ageing science.

I’ll wrap up by asking some ‘elephant in the room’ style ethical questions.

Michael Snyder Ageotypes

Michael Snyder: Four Ageotypes

Stanford Professor of Genetics Snyder measured multiple biomarkers over a five-year period to investigate how people age differently.

He found that those broad biological functions age at different rates.

Individuals can be grouped into four types, based on their primary site of ageing. These factors are dynamic. While they all correlate with chronological age, the rates vary between individuals.

An exciting use of this data is to identify molecules and pathways which differ between people aging in specific ways.

Here are the four Ageotypes:

  • Immune System
  • Metabolic Ageing
  • Hepatic (liver)
  • Nephrotic (kidney)

Kidney Ageing

Risk of Age-Related Chronic Conditions

Ageotypes develop conditions related to their primary ageing pathway.

For example, people with metabolic age higher than their chronological age are more likely to develop type 2 diabetes and have higher markers of blood sugar. Immune system ageing relates to propensity to suffer from infections.

Knowing which ageotype you are unlocks the potential for targeted interventions. These could be drugs, lifestyle changes or focus on your diet.

It raises the question of whether longevity drugs which work by triggering scarcity pathways (for example mTOR inhibitors) may help one ageotype more than another.

Sex Differences and Longevity

Women live longer than men on average.

This is true for all countries and economic classes – with the statistics going back more than 200 years.

When it comes to longevity drugs and treatments, there are sex differences – at least in animal populations.

Unfortunately, there is no clear pattern of which drugs work for which sex. Some drugs give female mice a longer life, and barely effect males, others show the opposite effect.

This research is showing promise. Every researcher knows the mantra, ‘mice are not mini people.’ That said, interactions between specific longevity drugs, hormones, IGF-1 and other molecules which differ between the sexes will answer important questions on the myriad interactions and pathways that affect ageing.

I’d like to see how sex differences in ageing work with the ageotypes. Is one sex more likely to express specific ageotypes? Are the pathways involved in them different between the sexes? And if so, would this mean different combinations of drugs, diet and lifestyle are required?

Women Outlive Men

Gene Expression and Ageotypes

APOE is a gene associated with Alzheimer’s disease – it provides an example of how gene variations affect the ageing process.

There are multiple forms of this gene. Most people have APOE3. If you have the APOE4 variant, you are significantly more likely to get Alzheimer’s and to develop it earlier than average. Two copies of this gene increase your risk further.

This paper explains the complexities.

APOE2 is rare. This variation provides protection in both developing Alzheimer’s and in later onset.

There are gene mutations associated with Parkinson’s disease, heart conditions, stroke risk, and hereditary cancer risk. There are also genes associated with the propensity for weight gain – and for more specific issues like inflammation response. The list of potential interactions with longevity drugs and treatments is huge.

Longevity Drugs affect exercise benefits

Ageotypes, Ethics and Personalised Longevity Treatments

Longevity research is still early – and still focused on broad-based interventions which can add years of healthy life to everyone.

I can see a time when treatments get more specific. When they are balanced to match the variable rate of ageing for different organs, pathways, and processes. Whether this remains as Snyder’s four ageotypes, or whether a different classification system is used is an open question.

There is an ethical minefield ahead:

  • What if a drug or intervention is found that only works for one sex?
  • What if that drug only works for individuals with a specific gene variant?
  • What if that gene variant is only found in a specific demographic or geographical area?
  • Should we treat these people, while every else gets to wait for the next breakthrough?


More Popular Longevity Science Articles:


Mark’s Blog





Share this article

Popular Articles